Evaluation of Ixekizumab Using Auto-Injector or Prefilled Syringe in Participants With Moderate to Severe Plaque Psoriasis (UNCOVER-A)

• ClinicalTrials.gov Identifier: NCT01777191
• Recruitment Status: Completed
• First Posted: January 28, 2013
• Results First Posted: May 26, 2016
• Last Update Posted: September 30, 2019
• Sponsor: Eli Lilly and Company
• Information provided by (Responsible Party): Eli Lilly and Company

Study Description

Brief Summary:

The purpose of this study is to evaluate the serum concentration of ixekizumab after administration using either prefilled syringe or auto-injector in participants with moderate to severe plaque psoriasis. Treatment period is followed by 40 weeks optional safety extension.

Condition or disease	Intervention/treatment	Phase
Plaque Psoriasis	Drug: Ixekizumab Auto-Injector; Drug: Ixekizumab Prefilled Syringe	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 204 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Pharmacokinetic Evaluations of Ixekizumab Following Subcutaneous Administration Using Prefilled Syringe or Auto-Injector in Patients With Moderate-to-Severe Plaque Psoriasis
• Study Start Date: March 2013
• Actual Primary Completion Date: May 2014
• Actual Study Completion Date: May 2015

Arms and Interventions

Arm	Intervention/treatment
Experimental: 80 mg Ixekizumab Auto-Injector; Ixekizumab administered by two 80 milligram (mg) subcutaneous (SC) injections at Week 0, then one 80 mg SC injection every 2 weeks (Q2W) at week 2, 4, 6, 8 and 10. Starting from Week 12, 80 mg Ixekizumab Prefilled Syringe was administered by one 80 mg SC injection every 4 weeks (Q4W).	Drug: Ixekizumab Auto-Injector; Administered SC by auto-injector; Other Name: LY2439821
Experimental: 80 mg Ixekizumab Prefilled Syringe; Ixekizumab administered by two 80 mg SC injections at Week 0, then one 80 mg SC injection Q2W at week 2, 4, 6, 8 and 10. Starting from Week 12, 80 mg Ixekizumab Prefilled Syringe was administered by one 80 mg SC injection Q4W.	Drug: Ixekizumab Prefilled Syringe; Administered SC by prefilled syringe; Other Name: LY2439821

Outcome Measures

Primary Outcome Measures :

1. Pharmacokinetics (PK): Maximum Serum Concentration (Cmax) by Drug Delivery Device [ Time Frame: Day 2, Day 4, Day 7, Day 10 and Day 14 (prior to Ixekizumab administration) ]
   Cmax by drug delivery device (prefilled syringe or auto-injector) of Ixekizumab, after the 160 mg starting dose was administered on Day 0.
2. PK: Area Under the Concentration Time Curve From Time Zero to Last Measured Concentration Value (AUC 0-[Tlast]) by Drug Delivery Device [ Time Frame: Day 2, Day 4, Day 7, Day 10 and Day 14 (prior to Ixekizumab administration) ]
   AUC 0-tlast by drug delivery device (prefilled syringe or auto-injector) of Ixekizumab, after the 160 mg starting dose was administered on Day 0. AUC 0-tlast is equal to AUC 0-14 days where the last time point was 14 days ± 24 hours.

Secondary Outcome Measures :

1. PK: Cmax of Ixekizumab by Site of Injection (Arm, Thigh or Abdomen) [ Time Frame: Day 2, Day 4, Day 7, Day 10 and Day 14 (prior to Ixekizumab administration) ]
   Cmax by site of injection of Ixekizumab, after the 160 mg starting dose was administered on Day 0.
2. PK: AUC 0-tlast by Site of Injection (Arm, Thigh or Abdomen) [ Time Frame: Day 2, Day 4, Day 7, Day 10 and Day 14 (prior to Ixekizumab administration) ]
   AUC 0-tlast by site of injection of Ixekizumab, after the 160 mg starting dose was administered on Day 0. AUC 0-tlast is equal to AUC 0-14 days where the last time point was 14 days ± 24 hours.
3. PK: Cmax by Body Weight [ Time Frame: Day 2, Day 4, Day 7, Day 10 and Day 14 (prior to Ixekizumab administration) ]
   Cmax by body weight of Ixekizumab, after the 160 mg starting dose was administered on Day 0. Body weight is defined by (Low: <80 kilogram (kg), Medium: 80-100 kg, or High: >100 kg).
4. PK: AUC 0-tlast by Body Weight [ Time Frame: Day 2, Day 4, Day 7, Day 10 and Day 14 (prior to Ixekizumab administration) ]
   AUC 0-tlast by body weight of Ixekizumab, after the 160 mg starting dose was administered on Day 0. AUC 0-tlast is equal to AUC 0-14 days where the last time point was 14 days ± 24 hours. Body weight is defined by (Low: <80 kg, Medium: 80-100 kg, or High: >100 kg).
5. Percentage of Participants Achieving a ≥75%, ≥ 90% and 100% Improvement in Psoriasis Area and Severity Index (PASI): Efficacy of Ixekizumab in Participants With Moderate to Severe Plaque Psoriasis. Measure: Psoriasis Area and Severity Index (PASI) [ Time Frame: Week 12 ]
   PASI combines assessments of the extent of body-surface involvement in 4 anatomical regions (head, trunk, arms, and legs) and the severity of desquamation, erythema, and plaque induration/infiltration (thickness) in each region, yielding an overall score of 0 or no Ps to 72 for the most severe disease. Participants achieving PASI 75, 90, or 100 are defined as having an improvement of at least 75%, 90%, or of 100%, respectively, in the PASI scores compared to baseline.
6. Percentage of Participants With a Static Physician Global Assessment (sPGA) (0,1): Efficacy of Ixekizumab in Participants With Moderate to Severe Plaque Psoriasis. Measure: Static Physician Global Assessment (sPGA) [ Time Frame: Week 12 ]
   The sPGA is the physician's determination of the participant's Psoriasis (Ps) lesions overall at a given time point. Lesions were categorized by descriptions for induration, erythema, and scaling. Participant's Ps was assessed as 0 (clear), 1 (minimal), 2 (mild), 3 (moderate), 4 (severe), or 5 (very severe). An sPGA responder was defined as having a post-baseline sPGA score of "0" or "1" with at least a 2-point improvement from baseline.
7. Percentage of Participants With a Static Physician Global Assessment (sPGA) (0) [ Time Frame: Week 12 ]
   The sPGA is the physician's determination of the participant's Ps lesions overall at a given time point. Lesions were categorized by descriptions for induration, erythema, and scaling. Participant's Ps was assessed as 0 (clear), 1 (minimal), 2 (mild), 3 (moderate), 4 (severe), or 5 (very severe).
8. Percentage of Device Operation Failures [ Time Frame: Baseline through Week 12 ]
   Device operation failure (that is, incomplete dose administration) was defined as an event during the treatment period (week 0 to week 12) when the participant indicated that a complete dose of ixekizumab was not delivered and/or the drug delivery device did not perform as expected per the directions for use.
9. Percentage of Participants With Anti-Ixekizumab Antibodies [ Time Frame: Baseline to Week 12 ]
   The percentage of participants with treatment-emergent positive anti-ixekizumab antibodies at anytime post-baseline were summarized by drug delivery device group. Percentage was calculated based on the number of evaluable participants and was calculated by number of participants with treatment-emergent positive anti-ixekizumab antibodies / number of evaluable participants * 100%.
10. SQAAQ Item Scores: Quality of Life and Outcome Assessments. Measures: Patient Reported Outcomes (PRO) [ Time Frame: Baseline, Week 4 and Week 8 ]
    The SQAAQ is a self-administered questionnaire which provides an assessment of ease of use and confidence with using a device to administer a subcutaneous injection of drug. Participants and injection assistants responded to questionnaire items using a 7-point Likert scale (from "Strongly Disagree" to "Strongly Agree"). 1 represents "Strongly Disagree" while 7 represents "Strongly Agree". The ease of use and confidence of ixekizumab subcutaneous administrations across drug delivery device groups were evaluated by SQAAQ item scores at each post baseline visit.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Present with chronic plaque psoriasis based on a confirmed diagnosis of chronic psoriasis vulgaris for at least 6 months prior to randomization
• At least 10% Body Surface Area (BSA) of Psoriasis at screening and at randomization
• Static Physician Global Assessment (sPGA) score of at least 3 AND Psoriasis Area and Severity Index (PASI) score of at least 12 at screening and at randomization
• Candidate for phototherapy and/or systemic therapy
• Men must agree to use a reliable method of birth control during the study
• Women must agree to use birth control or remain abstinent during the study and for at least 12 weeks after stopping treatment

Exclusion Criteria:

• Pustular, erythrodermic, and/or guttate forms of psoriasis
• History of drug-induced psoriasis
• Clinically significant flare of psoriasis during the 12 weeks prior to randomization
• Concurrent or recent use of any biologic agent
• Received systemic psoriasis therapy [such as psoralen and ultraviolet A (PUVA) light therapy] or phototherapy within the previous 4 weeks; or had topical psoriasis treatment within the previous 2 weeks prior to randomization
• Cannot avoid excessive sun exposure or use of tanning booths for at least 4 weeks prior to randomization and during the study
• Have participated in any study with interleukin-17 (IL-17) antagonists, including Ixekizumab
• Serious disorder or illness other than plaque psoriasis
• Serious infection within the last 3 months
• Breastfeeding or nursing (lactating) women

Contacts and Locations

Locations

United States, California

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Anaheim, California, United States, 92801

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Bakersfield, California, United States, 93309

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Santa Monica, California, United States, 90404

United States, Florida

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Miami, Florida, United States, 33144

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Ocala, Florida, United States, 34471

United States, Georgia

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Atlanta, Georgia, United States, 30327

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Newnan, Georgia, United States, 30263

United States, Illinois

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Arlington Heights, Illinois, United States, 60005

United States, Indiana

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Evansville, Indiana, United States, 47714

United States, Kentucky

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Louisville, Kentucky, United States, 40202

United States, Louisiana

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Lake Charles, Louisiana, United States, 70605

United States, Massachusetts

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Methuen, Massachusetts, United States, 01844

United States, Missouri

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Saint Louis, Missouri, United States, 63117

United States, Nebraska

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Omaha, Nebraska, United States, 68144

United States, New Hampshire

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Newington, New Hampshire, United States, 03801

United States, New Jersey

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East Windsor, New Jersey, United States, 08520

United States, New Mexico

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Albuquerque, New Mexico, United States, 87104

United States, North Carolina

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Greensboro, North Carolina, United States, 27408

United States, Pennsylvania

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Exton, Pennsylvania, United States, 19341

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Wyomissing, Pennsylvania, United States, 19610

United States, Utah

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Salt Lake City, Utah, United States, 84132

United States, Washington

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Seattle, Washington, United States, 98101

Puerto Rico

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Caguas, Puerto Rico, 00725

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Carolina, Puerto Rico, 00985

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Ponce, Puerto Rico, 00716

Sponsors and Collaborators

Eli Lilly and Company

Investigators

• Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST); Eli Lilly and Company

More Information

Publications of Results:

Callis Duffin K, Bagel J, Bukhalo M, Mercado Clement IJ, Choi SL, Zhao F, Gill A, Pangallo B, Shuler C, Mallbris L, Jackson K. Phase 3, open-label, randomized study of the pharmacokinetics, efficacy and safety of ixekizumab following subcutaneous administration using a prefilled syringe or an autoinjector in patients with moderate-to-severe plaque psoriasis (UNCOVER-A). J Eur Acad Dermatol Venereol. 2017 Jan;31(1):107-113. doi: 10.1111/jdv.13768. Epub 2016 Aug 8.

• Responsible Party: Eli Lilly and Company
• ClinicalTrials.gov Identifier: NCT01777191
• Other Study ID Numbers: 14728; I1F-MC-RHBL ( Other Identifier: Eli Lilly and Company )
• First Posted: January 28, 2013
• Results First Posted: May 26, 2016
• Last Update Posted: September 30, 2019
• Last Verified: September 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement.
• Supporting Materials: Study Protocol; Statistical Analysis Plan (SAP); Clinical Study Report (CSR)
• Time Frame: Data are available 6 months after the primary publication and approval of the indication studied in the US and EU, whichever is later. Data will be indefinitely available for requesting.
• Access Criteria: A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.
• URL: https://vivli.org/

Additional relevant MeSH terms:

Psoriasis; Skin Diseases, Papulosquamous; Skin Diseases; Ixekizumab; Dermatologic Agents